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The safety and short-term efficacy of laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy has not been demonstrated. The aim of the randomised Comparison of Open versus laparoscopic surgery for mid and low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was to compare open surgery with laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy. Between April 4, 2006, and Aug 26, 2009, patients with cT3N0–2 mid or low rectal cancer without distant metastasis after preoperative chemoradiotherapy were enrolled at three tertiary-referral hospitals. Patients were randomised 1:1 to receive either open surgery (n=170) or laparoscopic surgery (n=170), stratified according to sex and preoperative chemotherapy regimen. Short-term outcomes assessed were involvement of the circumferential resection margin, macroscopic quality of the total mesorectal excision specimen, number of harvested lymph nodes, recovery of bowel function, perioperative morbidity, postoperative pain, and quality of life. Analyses were based on the intention-to-treat population. Patients continue to be followed up for the primary outcome (3-year disease-free survival). This study is registered with ClinicalTrials.gov, number NCT00470951. Two patients (1·2%) in the laparoscopic group were converted to open surgery, but were included in the laparoscopic group for analyses. Estimated blood loss was less in the laparoscopic group than in the open group (median 217·5 mL [150·0–400·0] in the open group vs 200·0 mL [100·0–300·0] in the laparoscopic group, p=0·006), although surgery time was longer in the laparoscopic group (mean 244·9 min [SD 75·4] vs 197·0 min [62·9], p<0·0001). Involvement of the circumferential resection margin, macroscopic quality of the total mesorectal excision specimen, number of harvested lymph nodes, and perioperative morbidity did not differ between the two groups. The laparoscopic surgery group showed earlier recovery of bowel function than the open surgery group (time to pass first flatus, median 38·5 h [23·0–53·0] vs 60·0 h [43·0–73·0], p<0·0001; time to resume a normal diet, 85·0 h [66·0–95·0] vs 93·0 h [86·0–121·0], p<0·0001; time to first defecation, 96·5 h [70·0–125·0] vs 123 h [94·0–156·0], p<0·0001). The total amount of morphine used was less in the laparoscopic group than in the open group (median 107·2 mg [80·0–150·0] vs 156·9 mg [117·0–185·2], p<0·0001). 3 months after proctectomy or ileostomy takedown, the laparoscopic group showed better physical functioning score than the open group (0·501 [n=122] vs −4·970 [n=128], p=0·0073), less fatigue (−5·659 [n=122] vs 0·098 [n=129], p=0·0206), and fewer micturition (−2·583 [n=122] vs 4·725 [n=129], p=0·0002), gastrointestinal (−0·400 [n=122] vs 4·331 [n=129], p=0·0102), and defecation problems (0·535 [n=103] vs 5·327 [n=99], p=0·0184) in repeated measures analysis of covariance, adjusted for baseline values. Laparoscopic surgery after preoperative chemoradiotherapy for mid or low rectal cancer is safe and has short-term benefits compared with open surgery; the quality of oncological resection was equivalent. The National Cancer Center, South Korea.

\"Twin brothers believe they were born into an inseparable destiny, only to be betrayed by fate. Kim Hyung-cha is conscripted to serve as a student soldier during the Japanese occupation under conditions of severe cruelty, while his older twin, Kim Hyung-tae, who remained in the North after liberation, goes missing in the turbulence of the Korean War. Kim Hyungcha joins the allied forces and advances to the Yalu River with the war, where he miraculously finds his brother's family and manages to evacuate them to the South\"-- Publisher's description.

Compared with open resection, laparoscopic resection of rectal cancers is associated with improved short-term outcomes, but high-level evidence showing similar long-term outcomes is scarce. We aimed to compare survival outcomes of laparoscopic surgery with open surgery for patients with mid-rectal or low-rectal cancer. The Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial was an open-label, non-inferiority, randomised controlled trial done between April 4, 2006, and Aug 26, 2009, at three centres in Korea. Patients (aged 18–80 years) with cT3N0–2M0 mid-rectal or low-rectal cancer who had received preoperative chemoradiotherapy were randomly assigned (1:1) to receive either open or laparoscopic surgery. Randomisation was stratified by sex and preoperative chemotherapy regimen. Investigators were masked to the randomisation sequence; patients and clinicians were not masked to the treatment assignments. The primary endpoint was 3 year disease-free survival, with a non-inferiority margin of 15%. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00470951. We randomly assigned 340 patients to receive either open surgery (n=170) or laparoscopic surgery (n=170). 3 year disease-free survival was 72·5% (95% CI 65·0–78·6) for the open surgery group and 79·2% (72·3–84·6) for the laparoscopic surgery group, with a difference that was lower than the prespecified non-inferiority margin (–6·7%, 95% CI −15·8 to 2·4; p<0·0001). 25 (15%) patients died in the open group and 20 (12%) died in the laparoscopic group. No deaths were treatment related. Our results show that laparoscopic resection for locally advanced rectal cancer after preoperative chemoradiotherapy provides similar outcomes for disease-free survival as open resection, thus justifying its use. National Cancer Center, South Korea.

North Korea is perilously close to developing strategic nuclear weapons capable of hitting the United States and its allies in East Asia. Since their first nuclear test in 2006, North Korea has struggled to perfect delivery systems, but Kim Jong-un's regime now appears to be close. Sung Chull Kim, Michael Cohen, and the contributors to this volume contend that the time to prevent North Korea from getting this capability is virtually over, and instead scholars and policymakers must turn their attention to how to deter North Korea. The United States, South Korea, and Japan must also come to terms with the fact their North Korea will be able to deter them with its nuclear arsenal. How will the erratic Kim Jong-un behave when North Korea does develop the capability to hit medium- and long-range targets with nuclear weapons; how will the United States, South Korea, and China respond; and what will this mean for regional stability in the short term and long term? The international group of authors in this volume address these questions and offer a timely analysis of the consequences of an operational North Korean nuclear capability for international security.

Patients with EGFR-mutated non-small-cell lung cancer (NSCLC) given EGFR tyrosine kinase inhibitors (TKIs) inevitably become resistant to first-generation or second-generation drugs. We assessed the safety, tolerability, pharmacokinetics, and activity of lazertinib—an irreversible, third-generation, mutant-selective, EGFR TKI—in patients with advanced NSCLC progressing after EGFR TKI therapy. This first-in-human, open-label, multicentre, phase 1–2 study had three parts: dose escalation, dose expansion, and dose extension; here, we report results on dose escalation and dose expansion. The study was done in 14 hospitals in Korea. Eligible patients were aged 20 years or older and had advanced NSCLC harbouring an activating EGFR mutation and progressing after first-generation or second-generation EGFR TKI treatment, a defined tumour T790M mutation status, an Eastern Cooperative Oncology Group performance status of 0–1, at least one measurable extracranial lesion, defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and adequate organ function. Patients were enrolled to seven dose-escalation cohorts according to a rolling six design; five cohorts were expanded. Patients were given oral lazertinib 20 mg, 40 mg, 80 mg, 120 mg, 160 mg, 240 mg, or 320 mg once daily continuously in 21-day cycles. Primary endpoints were safety and tolerability and secondary endpoints included objective response in evaluable patients. This study is registered with ClinicalTrials.gov, NCT03046992, and the phase 2 extension study is ongoing. Between Feb 15, 2017, and May 28, 2018, 127 patients were enrolled into the dose escalation group (n=38) and dose expansion group (n=89). No dose-limiting toxicities occurred. There was no dose-dependent increase in adverse events. The most commonly reported adverse events were grade 1–2 rash or acne (in 38 [30%] of 127 patients) and pruritus (in 34 [27%]). Grade 3 or grade 4 adverse events occurred in 20 (16%) patients, with the most common being grade 3 pneumonia (four [3%]). Treatment-related grade 3 or 4 adverse events occurred in four (3%) patients; treatment-related serious adverse events were reported in six patients (5%). There were no adverse events with an outcome of death and no treatment-related deaths. The proportion of patients achieving an objective response by independent central review assessment was 69 (54%; 95% CI 46–63) of 127. Lazertinib had a tolerable safety profile and showed promosing clinical activity in patients with NSCLC progressing on or after EGFR TKI therapy. Our findings provide a rationale for further clinical investigations. Yuhan Corporation.

In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients’ long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR 4.5 ; BCR-ABL ⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.

Spin–orbit coupling results in technologically-crucial phenomena underlying magnetic devices like magnetic memories and energy-efficient motors. In heavy element materials, the strength of spin–orbit coupling becomes large to affect the overall electronic nature and induces novel states such as topological insulators and spin–orbit-integrated Mott states. Here we report an unprecedented charge-ordering cascade in IrTe 2 without the loss of metallicity, which involves localized spin–orbit Mott states with diamagnetic Ir 4+ –Ir 4+ dimers. The cascade in cooling, uncompensated in heating, consists of first order-type consecutive transitions from a pure Ir 3+ phase to Ir 3+ –Ir 4+ charge-ordered phases, which originate from Ir 5 d to Te 5 p charge transfer involving anionic polymeric bond breaking. Considering that the system exhibits superconductivity with suppression of the charge order by doping, analogously to cuprates, these results provide a new electronic paradigm of localized charge-ordered states interacting with itinerant electrons through large spin–orbit coupling. The influence of spin–orbit coupling on itinerant electrons underlies the formation of spin–orbit Mott states. Here, the authors demonstrate a temperature-hysteretic cascade between charge-ordered phases stabilized by localized 5 d spin–orbit Mott dimer states in metallic iridium ditelluride.